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921.
Wright FA Strug LJ Doshi VK Commander CW Blackman SM Sun L Berthiaume Y Cutler D Cojocaru A Collaco JM Corey M Dorfman R Goddard K Green D Kent JW Lange EM Lee S Li W Luo J Mayhew GM Naughton KM Pace RG Paré P Rommens JM Sandford A Stonebraker JR Sun W Taylor C Vanscoy LL Zou F Blangero J Zielenski J O'Neal WK Drumm ML Durie PR Knowles MR Cutting GR 《Nature genetics》2011,43(6):539-546
A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder. 相似文献
922.
Gui Y Guo G Huang Y Hu X Tang A Gao S Wu R Chen C Li X Zhou L He M Li Z Sun X Jia W Chen J Yang S Zhou F Zhao X Wan S Ye R Liang C Liu Z Huang P Liu C Jiang H Wang Y Zheng H Sun L Liu X Jiang Z Feng D Chen J Wu S Zou J Zhang Z Yang R Zhao J Xu C Yin W Guan Z Ye J Zhang H Li J Kristiansen K Nickerson ML Theodorescu D Li Y Zhang X Li S Wang J Yang H Wang J Cai Z 《Nature genetics》2011,43(9):875-878
Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer. 相似文献
923.
Genome-wide association study of leaf architecture in the maize nested association mapping population 总被引:13,自引:0,他引:13
Tian F Bradbury PJ Brown PJ Hung H Sun Q Flint-Garcia S Rocheford TR McMullen MD Holland JB Buckler ES 《Nature genetics》2011,43(2):159-162
US maize yield has increased eight-fold in the past 80 years, with half of the gain attributed to selection by breeders. During this time, changes in maize leaf angle and size have altered plant architecture, allowing more efficient light capture as planting density has increased. Through a genome-wide association study (GWAS) of the maize nested association mapping panel, we determined the genetic basis of important leaf architecture traits and identified some of the key genes. Overall, we demonstrate that the genetic architecture of the leaf traits is dominated by small effects, with little epistasis, environmental interaction or pleiotropy. In particular, GWAS results show that variations at the liguleless genes have contributed to more upright leaves. These results demonstrate that the use of GWAS with specially designed mapping populations is effective in uncovering the basis of key agronomic traits. 相似文献
924.
目的观察外源性硫化氢对嗜铬细胞瘤细胞β-位淀粉样前体蛋白裂解酶1(BACE1)的调节作用,进而探讨其对淀粉样前体蛋白/β-位淀粉样蛋白代谢途径的影响。方法用硫氢化钠作外源性H2s供体,实验设空白对照组、NaHs50μmol/L组、NaHS100μmol/L组和NariS200μmol/L组,按分组浓度处理PC12细胞24h后,RT-PCR和Western blot法检测细胞内BACE1 mRNA及蛋白表达,并用Western blot法继而检测APP代谢过程中关键蛋白APP、C99、C83表达变化,EusA法检测细胞培养液中AB40和AB42水平。结果NaHS在实验浓度范围内从基因与蛋白两个水平上呈剂量依赖性下调BACE1表达,并下调C99、Ap40和Ap42蛋白表达,上调C83蛋白,各NaHS组分别与对照组比较,差别均有统计学意义(P〈0.05),而对APP蛋白表达没有影响,各组间比较差别无显著性(P〉0.05)。结论外源性H2s具有通过调节PC12细胞BACE1表达下调APP/Aβ代谢的作用。 相似文献
925.
针对MEMS压力传感器封装关键技术,从结构仿真和工艺参数等方面研究了一款压力传感器的硅玻静电键合问题,旨在减小封接对压力传感器芯片输出性能的影响。设计并制作键合装置,进而完成实验,最终优化键合温度,电压等参数值,验证最佳温度350~C,理想电压范围500~900V。 相似文献
926.
目的通过胰岛素和磷脂酰肌醇-3激酶(P13K)抑制剂渥曼青霉素(wortmannin)对P13K/丝氨酸苏氨酸蛋白激酶(P13K/Akt)信号通路的激活和抑制作用,观察P13K/Akt信号通路对海马神经元β-淀粉样前体蛋白裂解酶1(BACEl)mRNA水平表达的影响。方法20只sD大鼠随机分为空白对照组、假手术组、胰岛素组和渥曼青霉素组,海马立体定向注射胰岛素和P13K抑制剂渥曼青霉素。逆转录一聚合酶链反应(RT-PCR)检测P13K/Akt信号传导下游蛋白Akt以及BACEImRNA水平。结果注射胰岛素的海马P13K信号通路下游信号分子:AktmRNA表达上调(分别较空白和阴性对照组P=0.047,P=0.002),而BACElmRNA表达下调(分别较空白和阴性对照组P=0.004,P=0.01)。渥曼青霉素组的P13K下游信号分子AktmRNA表达明显被抑制(分别较空白和阴性对照组P=0.002,P=0.039),同时BACEImRNA的表达较对照组上调(分别较空白和阴性对照组P=0.039,P=0.018)。结论胰岛素信号通路P13K/AM可以调节BACEl的转录水平参与阿尔茨海默病的发病机制。 相似文献
927.
In this article, an optimal switching integrity attack problem is investigated to study the response of feedback control systems under attack. The authors model the malicious attacks on sensors as additive norm bounded signals. The authors consider an attacker who is only capable of launching attacks to limited number of sensors once a time and changing the combinations of attacked sensors all over the time. The objective of this paper is to find the optimal switching sequence of these combinations and the optimal attack input. The authors solve this problem by transforming it into a traditional optimal control problem with new control variables vary continuously in the range [0, 1]. The optimal solutions of the new control variables are of bang-bang-type. Therefore, an algebraic switching condition and an optimal attack input can be obtained. Finally, numerical results are provided to illustrate the effectiveness of the methods. 相似文献
928.
Journal of Systems Science and Complexity - Weispfenning in 1992 introduced the concepts of comprehensive Gröbner system/basis of a parametric polynomial system, and he also presented an... 相似文献
929.
Yun Liu Zeyao Zhu Idy H. T. Ho Yujian Shi Yuxin Xie Jianzhen Li Yong Zhang Matthew T. V. Chan Christopher H. K. Cheng 《Cellular and molecular life sciences : CMLS》2017,74(13):2503-2511
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development. Our findings establish that Cre/loxP-mediated tissue-specific gene knockout could be achieved using this BACK strategy and that canonical microRNAs play important roles in early embryonic development in zebrafish. 相似文献
930.
伊隆迈多金属矿位于西南"三江"义敦岛弧的南段东部斑岩成矿带中。以地质勘查资料为依据,通过开展物探工作获得了以下成果:60线长剖面的重力测量在2 780~4 500区间获得了明显的相对低重力异常,推断该区间深部存在隐伏中-酸性岩体;激电中梯扫面工作在测区东西两侧各获得一个北北西向展布的高极化率条带,推断这两个条带与玄武岩和黄铁矿化凝灰岩有关;利用放射性伽马总量测量对平面上石英二长斑岩脉的走向延伸情况进行了推测;利用高密度电法、激电测深及音频大地电磁测深对该区深部的地质特征进行了推测,根据高密度电法工作成果推断,石英二长斑岩在埋深30m范围内产状陡倾略偏南西,闪长玢岩前期侵入灰岩地层并形成较陡的接触面,石英二长斑岩在后期侵位于闪长玢岩与灰岩的接触面。 相似文献